Insulin Degludec: Pharmacokinetic Properties in Subjects with Hepatic Impairment

• Published in: Clinical drug investigation Vol. 34; no. 2; pp. 127 - 133
• Main Authors: Kupčová, Viera, Arold, Gerhard, Roepstorff, Carsten, Højbjerre, Malene, Klim, Søren, Haahr, Hanne
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.02.2014; Springer Nature B.V
• Subjects: Adult; Area Under Curve; Female; Humans; Hypoglycemic Agents - pharmacokinetics; Injections, Subcutaneous; Insulin, Long-Acting - pharmacokinetics; Internal Medicine; Liver Diseases - physiopathology; Liver Function Tests; Male; Medicine; Medicine & Public Health; Middle Aged; Original; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy; Severity of Illness Index; Young Adult; Insulin Aspart; Insulin Detemir; Insulin Glargine; Hepatic Impairment; Insulin Lispro
• ISSN: 1173-2563; 1179-1918; 1179-1918
• DOI: 10.1007/s40261-013-0154-1

Background and Objective Insulin degludec is a basal insulin with a slow and distinct absorption mechanism resulting in an ultra-long, flat, and stable pharmacokinetic profile in patients with diabetes mellitus. The aim of this study was to examine the effect of hepatic impairment on the single-dose pharmacokinetics of insulin degludec. Methods Twenty-four subjects, allocated to one of four groups ( n  = 6 per group) based on level of hepatic impairment (normal hepatic function, Child–Pugh grade A, B, or C), were administered a single subcutaneous dose of 0.4 U/kg insulin degludec. Blood samples up to 120 h post-dose and fractionated urine samples were collected to measure pharmacokinetic parameters. Results No difference was observed in pharmacokinetic parameters [area under the 120-h serum insulin degludec concentration–time curve (AUC 120 h ), maximum insulin degludec concentration ( C max ), and apparent clearance (CL/ F )] for subjects with impaired versus normal hepatic function after a single dose of insulin degludec. The geometric mean [coefficient of variation (CV) %] AUC 120 h values were 89,092 (16), 83,327 (15), 88,944 (23), and 79,846 (19) pmol·h/L for normal hepatic function and mild, moderate, and severe hepatic impairment, respectively. Simulated steady-state insulin degludec pharmacokinetic profiles showed an even distribution of exposure across a 24-h dosing interval regardless of hepatic function status. Conclusions The ultra-long pharmacokinetic properties of insulin degludec were preserved in subjects with hepatic impairment and there were no statistically significant differences in absorption or clearance compared with subjects with normal hepatic function.